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Biomedical subjects

D F Moore

Publications and source records attributed to D F Moore.

At least 19 recordsLinked to original sources

Glutathione S-transferase activity and glutathione S-transferase mu expression in subjects with risk for colorectal cancer.

The glutathione S-transferases (alpha, mu, and pi), a family of Phase II detoxication enzymes, play a critical role in protecting the colon mucosa by catalyzing the conjugation of dietary carcinogens with glutathione. We investigated the efficacy of using the glutathione S-transferase (GST) activity of blood lymphocytes and GST-mu expression as biomarkers of risk for colorectal cancer. GST activity was measured in the blood lymphocytes of control individuals (n = 67) and in the blood lymphocytes (n = 60) and colon tissue (n = 34) of individuals at increased risk for colon cancer. Total GST activity was determined spectrophotometrically with the use of 1-chloro-2,4-dinitrobenzene as a substrate. The ability to express the um subclass of GST was determined with the use of an ELISA. Although interindividual variability in the GST activity of blood lymphocytes was greater than 8-fold (range, 16.7-146.8 nmol/min/mg), the GST activity of blood lymphocytes and colon tissue within an individual was constant over time and was unrelated to sex, age, or race. The GST activity of blood lymphocytes from high-risk individuals was significantly lower than that of blood lymphocytes from control individuals (P < or = 0.004). No association was observed between the frequency of GST-mu phenotype and risk for colorectal cancer. Blood lymphocytes from high-risk individuals unable to express GST-mu had lower levels of GST activity than did those from control subjects with the GST-mu null phenotype; however, this difference was significant in male subjects only (P < or = 0.006). Analysis of paired samples of blood lymphocytes and colon tissue indicated a strong correlation between the GST activity of the two tissue types (Spearman's rank correlation, r = 0.87; P < or = 0.0001). The GST activity of blood lymphocytes may be used to identify high-risk individuals with decreased protection from this Phase II detoxication enzyme who may benefit from clinical trials evaluating GST modulators as chemopreventive agents for colorectal cancer. The GST activity of blood lymphocytes may also be used in colorectal cancer chemoprevention trials to monitor the responsiveness of colon tissue to regimens that modify Phase II detoxication enzymes.

Adult

Cancer in families with systemic sclerosis.

In recent reports, researchers described an increased incidence of cancer in patients with systemic sclerosis (SScl). For this article, the authors investigated the frequencies of cancer in first-degree relatives of patients with SScl in a case-control family study. Information was obtained by personal interview of the probands. Fifty-three subjects with cancer were reported among 814 relatives of patients, compared with 17 subjects among 860 relatives of age- and sex-matched control subjects (age and sex adjusted odds ratio = 3.79, 95% confidence interval = 2.16-6.66, P < 0.001). Forty-six patients (27.7%) had one or more relatives with cancer, compared with 15 control subjects (9%). Within the limitations of the methods used, the researchers found an increased risk for cancer in first-degree relatives of patients with SScl. This suggests that a common genetic or environmental factor may be involved in the development of both cancer and SScl.

Adult

A phase II trial of oral etoposide with mitoxantrone and ifosfamide/mesna consolidated with intravenous etoposide, methylprednisolone, high-dose arabinoside, and cisplatin as salvage therapy for relapsing and/or refractory lymphomas.

PURPOSE: To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) as consolidation therapy after complete or partial responses (CR or PR, respectively) or after crossover therapy for progressive disease. METHODS: Patients received MINE(o) consisting of mesna, 1.33 g/m2 infused over 1 hour daily x 3 followed 4 hours later by oral mesna at 500 mg; ifosfamide, 1.33 g/m2 infused over 1 hour daily x 3; mitoxantrone, 8 mg/m2 intravenously on day 1, and oral VP-16, 30 mg/m2 daily x 13. The ESHAP regimen consisted of intravenous VP-16, 40 mg/m2 infused over 2 hours daily x 4; methylprednisolone, 500 mg intravenously daily x 4; cytosine arabinoside, 1.5 g/m2 infused over 3 hours on day 4; and cisplatin, 25 mg/m2 given as a continuous 24-hour infusion daily x 4. Statistical analysis was performed using the 2-stage design described by Simon. For the oral VP-16 regimen to be of interest, at least 36% patients had to achieve a complete remission. RESULTS: The overall response rate achieved with MINE(o) was 40% (15% CR, 25% PR). Seven patients with prior exposure to cytosine arabinoside and cisplatin (AP) received MINE(o) alone of whom only one achieved a response (CR). Thirteen patients without prior exposure to AP received consolidation (2 patients) or crossover (11 patients) therapy with ESHAP. Crossover therapy with ESHAP further improved the response in only two of five patients with partial response to MINE(o) and none of six patients who failed MINE(o). Median response duration for the patients who received MINE(o)/ESHAP was 12 weeks (range, 4-55 weeks). CONCLUSIONS: Oral VP-16 combined with ifosfamide/mesna and mitoxantrone at the doses and schedules indicated has little activity against relapsed and/or refractory lymphomas. Crossover therapy with ESHAP did not further improve the response rate. The duration of response after MINE(o)/ESHAP was short.

Adolescent

Phase II trial of intravenous melphalan in advanced colorectal carcinoma.

BACKGROUND: Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a phase II study to determine the efficacy of administering intravenous melphalan at doses that do not require BMT support in patients with advanced colorectal adenocarcinoma. PATIENTS AND METHODS: Fifteen patients with histologically proven, bidimensionally measurable disease were treated. The starting dose of melphalan was 30 mg/m2, with dose escalation permitted. RESULTS: No objective responses were observed. Toxic effects were primarily reversible granulocytopenia and thrombocytopenia. There were no treatment-associated deaths. CONCLUSION: Melphalan's lack of efficacy at the doses administered does not disprove the steep chemotherapy dose-response relationship postulated for many solid tumors. However, we feel that it is unlikely that repetitive courses of high dose melphalan with autologous BMT support will be a practical approach to the management of advanced colorectal adenocarcinoma.

Adenocarcinoma

Pica, iron deficiency, and the medical history.

We describe two new forms of pica associated with iron deficiency and a new variant of a third. Previous reports on pica are tabulated. The value of a sympathetic, nonjudgmental approach to eliciting the medical history is emphasized.

Adult

Phase II trial of edatrexate in patients with advanced hepatocellular carcinoma.

BACKGROUND: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin, or 10-EDAM) has demonstrated greater activity than methotrexate has against murine tumors and human tumor xenografts. Phase II trials of edatrexate have already demonstrated its activity against breast, lung, and head and neck carcinomas. A phase II trial of edatrexate was conducted in patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated unresectable hepatocellular carcinoma were enrolled on the study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously. The treatment course was repeated every 6 weeks. Tumor response was evaluated by computerized tomographic scan after 2 courses. RESULTS: No complete or partial responses were observed in this trial. Two minor responses, each lasting less than 12 weeks, were observed. Twelve patients had elevated serum alpha-fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients experienced a > or = 25% decrease in the level of this tumor marker; 3 of the 4 had a > 50% reduction in AFP level. Grade 3 and 4 toxic effects were granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions, fatigue, anorexia, and diarrhea. CONCLUSIONS: Edatrexate administered at this dose and schedule appears to have little therapeutic efficacy against advanced hepatocellular carcinoma.

Adult

Targeted HIV seroprevalence among Vietnamese in southern California.

OBJECTIVE: The prevalence of HIV among southern California Vietnamese is unknown. We collected seroprevalence data on targeted Vietnamese in Orange County, California who may be at risk for HIV infection. METHODS: The assumption of elevated risk was based on rates of infection reported among other U.S. groups. Vietnamese (N = 874) from six county sites were tested during 1992: (1) attendees at county HIV/STD clinics and (2) IDU program; (3) male inmates of the county jail and (4) of a juvenile detention centre; (5) males in a driving under the influence of alcohol (DUI) remedial program; and (6) patients for nonpregnancy-related syphilis screening. RESULTS: The number of cases detected and risk factors were: (1) county HIV/STD clinics--5/223 (2.3%), all men who had sex with men; (2) men's jail--1/122 (0.8%), risk factors unknown; (3) juvenile hall--1/145 (0.7%), risk factors unknown; (4) IDU program--0/33; (5) syphilis screening--0/284; and (6) DUI program--0/67. CONCLUSIONS: HIV infection exists among southern California Vietnamese, and men who have sex with men appear to be at a risk for HIV infection similar to others practicing high risk behaviors in the U.S. population. Preventive education needs to be targeted explicitly at these individuals.

Adult

Effect of educational program on compliance with glove use in a pediatric emergency department.

OBJECTIVE: To investigate the effect of an educational program on compliance with glove use in a pediatric emergency department. DESIGN: Without their knowledge, participants were observed for routine use of gloves during vascular access procedures before and after an educational program. Participants with up to 3 years' vascular access experience were defined as less experienced and those with 4 or more years' experience were defined as more experienced. Their success rates performing vascular access procedures with and without wearing gloves were also monitored. SETTING: Inner-city pediatric hospital emergency department. PARTICIPANTS: Twenty-three emergency department registered nurses. INTERVENTIONS: A 30-minute lecture with slides, written materials, and posters addressing the reasons and need for universal precautions, and recommended methods of barrier precautions to prevent skin and mucous membrane exposure when handling sharp instruments. MEASUREMENTS/MAIN RESULTS: For the less experienced registered nurses, the compliance rate before the educational program was 70% and remained at about 93% afterward. For the more experienced registered nurses, the compliance rate before the program was only 15%. After the program, this compliance rate rose to 93%, but declined to only 50% by the fifth month. The registered nurses' success rate on the first attempt at vascular access while wearing gloves was 75% compared with 70% without gloves. CONCLUSION: Educational programs can result in a clinically significant increase in glove use by pediatric emergency department registered nurses. Long-term improvement was less pronounced for the group of more experienced registered nurses. We also observed that glove use does not appear to interfere with the proficient performance of vascular access procedures.

Bloodletting

Phase II study of gemcitabine in advanced colorectal adenocarcinoma.

A phase II trial of gemcitabine (difluorodeoxycytidine) was conducted in 14 patients with advanced colorectal adenocarcinoma. Gemcitabine was administered intravenously over 30 minutes at weekly intervals for 3 consecutive weeks each month. The starting dose was 800 mg/m2, with dose escalation as tolerated. No complete or partial response were observed. Ten patients experienced progressive disease while on therapy. Toxic effects were primarily hematologic in nature. Grade 3 toxicities included leukopenia (one patient at 1000 mg/m2), granulocytopenia (two patients at 800 mg/m2), anemia (two patients at 800 mg/m2), and myalgia (one patient at 800 mg/m2). No grade 4 toxic effects or treatment-associated deaths were observed. Gemcitabine, at the doses and schedule used in this study, did not demonstrate activity against advanced colorectal adenocarcinoma.

Adenocarcinoma

Phase I study of 5-fluorouracil with folinic acid combined with recombinant human granulocyte-macrophage colony-stimulating factor.

A Phase I study was conducted to determine whether the addition of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to a combined 5-fluorouracil (5-FU) and folinic acid (FA) regimen would allow an escalated starting dose of 5-FU. FA (500 mg/m2) was administered as a 2-hour infusion on days 1 through 5, with 5-FU administered as a bolus injection 1 hour after the initiation of FA. Fifteen patients were enrolled in the trial; six were entered at a dose level of 375 mg/m2 of 5-FU, six at 450 mg/m2, and three at 540 mg/m2. rhGM-CSF was administered subcutaneously on days 6 through 15. A course of therapy was repeated every 28 days. Serious toxicity was observed at 450 mg/m2, with two patients developing grade 3 mucositis and one, grade 4 mucositis. Dose-limiting toxicity occurred at 540 mg/m2, at which point three patients developed grade 4 mucositis. One patient with metastatic colon cancer who received 5-FU at 540 mg/m2 achieved a partial response. Because of this persistent mucositis, the addition of rhGM-CSF used in this schedule would not allow an increased starting dose of 5-FU.

Adult

Isolation of Mycobacterium thermoresistibile following augmentation mammaplasty.

This is the first case report of a Mycobacterium thermoresistibile infection following augmentation mammaplasty and is the fourth human case report of M. thermoresistibile infection. Antimicrobial susceptibility results determined by a modified proportion method using a 3-day incubation were the same as those determined by the standard 3-week assay.

Adult

Modulation of fluorouracil with recombinant alfa interferon: M. D. Anderson Clinical trial.

Clinical trials have been initiated examining the combination of fluorouracil (5-FU) and recombinant interferon alfa-2a (rIFN-2a) in the treatment of advanced colorectal carcinomas. An early trial reported a response rate of 76%, encouraging further investigation. Clinical trials have used 5-FU administered as a continuous intravenous infusion, 750 mg/m2 per day for 5 consecutive days, followed by weekly bolus administration of 5-FU 750 mg/m2. Recombinant interferon alfa-2a, 9 million units, was administered subcutaneously three times weekly. Of 45 evaluable patients treated at The University of Texas M. D. Anderson Cancer Center, a response rate of 35% (95% confidence interval, 22%, 50%) was observed. Twenty-five percent of patients developed grade 4 toxicity and 82% developed grade 3 toxicity. The median survival was 16 months. Investigation of this combination will require randomized trials to further assess activity in relation to alternative treatments.

Antineoplastic Combined Chemotherapy Protocols

Robust estimation of the variance in moment methods for extra-binomial and extra-Poisson variation.

When faced with data in the form of overdispersed counts or proportions, moment methods allow consistent parameter estimation when only the form of the mean and variance is specified. If the variance form is misspecified, these methods still yield consistent parameter estimates, though with lower efficiency, and the variances of the estimates will be inconsistent. A variance correction is available that yields consistent variance estimates in these circumstances. The asymptotic and small-sample efficiencies of this correction are calculated, and its performance under variance misspecification is studied. A group-randomized breast self-examination prevention study that is now underway serves as a focal point for the study of these properties. The use of the variance correction in modelling is illustrated on a teratology data set.

Analysis of Variance

Clinical trials of fluorouracil with alpha-interferon in advanced colorectal carcinomas.

Three clinical trials have been conducted with fluorouracil (5-FU) and recombinant interferon alfa-2a (rIFN-alpha 2a) in the treatment of advanced colorectal carcinoma. The regimen consisted of 5-FU (750 mg/m2/d) as an intravenous continuous infusion for 5 consecutive days followed by a week's rest. Weekly bolus 5-FU (750 mg/m2) was subsequently administered. Nine million units of rIFN-alpha 2a was administered subcutaneously three times weekly. The initial clinical trial conducted by investigators from the Albert Einstein Cancer Center (New York, NY) reported a 76% response rate with 13 of 17 patients responding. When this clinical trial was extended to 32 patients, 20 patients (63%) achieved partial responses. Investigators from the University of Texas M.D. Anderson Cancer Center (Houston, TX) enrolled 45 evaluable patients and reported 15 partial responses and one clinical complete response (response rate, 36%). A similar trial was conducted at Memorial Sloan-Kettering Cancer Center (New York, NY) with nine of 35 patients (26%) experiencing partial responses. Grades 3 to 4 toxicities in these three trials included mucositis, diarrhea, leukopenia, and neurotoxicity. Four treatment-related deaths were reported, with three of these deaths ascribed to profuse watery diarrhea associated with leukopenia. Current randomized trials are comparing this regimen with 5-FU plus folinic acid. Future strategies will examine alternative schedules of 5-FU with interferon, and will attempt to better define the mechanism of interaction.

Carcinoma

Rapid herpes simplex virus detection in clinical samples submitted to a state virology laboratory.

Of 16,779 specimens received for herpes simplex virus (HSV) isolation since 1982, 4,465 (26.6%) were positive for HSV by either standard tissue culture or an antigen detection system (peroxidase-antiperoxidase; PAP). The overall isolation rate for genital vesicle specimens was lower (26.1%) than that for nongenital specimens (29.3%). Monthly isolation rates ranged from 19 to 32% for genital specimens and from 20 to 44% for nongenital specimens. Increasing demands for HSV isolation led to comparison of tissue culture with PAP. In the first comparison, HSV was isolated in single human fibroblast cell cultures from 1,019 of 4,261 specimens (23.9%), whereas single human fibroblast wells stained at 24 and 72 h postinoculation were PAP positive for 1,007 of 4,261 specimens (23.6%). In the second comparison, HSV was isolated from 225 of 1,026 (21.9%) specimens and duplicate human foreskin fibroblast cell wells stained at 24 and 72 h were PAP positive in 241 of 1,026 (23.5%). With the dual-well PAP system, all results were reported within 72 h, approximately 70% of positives were reported within 24 h, and considerable savings in time and materials resulted.

Antigens, Viral